The biological actions of the insulin-like growth factors, IGF-I and IGF-II, are mediated by the ligand-induced activation of the IGF-I receptor (IGF-IR), a transmembrane heterotetramer linked to the ras-raf-mitogen-activated protein kinase (MAPK) and phosphatidyl inositol 3 kinase (PI3K)-protein kinase B (PKB)/Akt signal transduction cascades. The Wilms' tumor suppressor gene (wt1) encodes a zinc finger transcription factor, WT1, which has been implicated in various cellular processes including proliferation, differentiation and apoptosis. In the present study we demonstrated that IGF-I modulates the WT1 gene expression in neurally derived PC12 cells in a dose- and time-dependent manner. This effect was mediated through both the MAPK and PI3-kinase signaling pathways, as shown by the ability of the specific inhibitors UO126 and LY294002 to abrogate IGF-I action. Moreover, using RT-PCR and transient transfection assays, we demonstrated that the IGF-I effect was associated with corresponding changes in WT1 mRNA levels and WT1 promoter activity. In addition, the results of the present study revealed that high WT1 levels were associated with the induction of apoptosis, whereas low WT1 levels were correlated with the inhibition of apoptosis, as demonstrated by poly ADP ribose polymerase (PARP) cleavage, Bax expression, Annexin V-FITC staining, and by the use of antisense oligonucleotides against WT1. In summary, our results show that the wt1 gene is a novel target for IGF-I action in neurally derived cells.

译文

胰岛素样生长因子igf-i和igf-ii的生物学作用是由配体诱导的igf-i受体 (igf-ir) 激活介导的,与ras-raf-有丝分裂原活化蛋白激酶 (MAPK) 和磷脂酰肌醇3激酶 (PI3K)-蛋白激酶B (PKB)/Akt信号转导级联连接的跨膜异四聚体。Wilmss的肿瘤抑制基因 (wt1) 编码锌指转录因子WT1,该因子与各种细胞过程有关,包括增殖,分化和凋亡。在本研究中,我们证明igf-i以剂量和时间依赖性方式调节神经源性PC12细胞中WT1基因的表达。这种作用通过MAPK和PI3-kinase信号通路介导,如特异性抑制剂UO126和LY294002消除igf-i作用的能力所示。此外,使用rt-pcr和瞬时转染分析,我们证明了igf-i效应与WT1 mRNA水平和WT1启动子活性的相应变化有关。此外,本研究的结果表明,高WT1水平与诱导凋亡有关,而低WT1水平与抑制凋亡有关,如聚ADP核糖聚合酶 (PARP) 切割,Bax表达,Annexin V-FITC染色,并通过使用针对wt1的反义寡核苷酸。总之,我们的结果表明wt1基因是神经源性细胞中igf-i作用的新靶标。

+1
+2
100研值 100研值 ¥99课程
检索文献一次
下载文献一次

去下载>

成功解锁2个技能,为你点赞

《SCI写作十大必备语法》
解决你的SCI语法难题!

技能熟练度+1

视频课《玩转文献检索》
让你成为检索达人!

恭喜完成新手挑战

手机微信扫一扫,添加好友领取

免费领《Endnote文献管理工具+教程》

微信扫码, 免费领取

手机登录

获取验证码
登录